Vemurafenib doesn't shrink BRAF-mutated colorectal tumors, but a regimen that also includes irinotecan and cetuximab improves vemurafenib's effectiveness, more than doubling progression-free survival in patients with metastatic tumors.
The studies were divided into five groups: (1) distribution of KRAS/BRAF mutations in distal and proximal colorectal cancer, the summary OR value was 1.24 versus 4.03, (2) distribution of KRAS/BRAF mutations in CIMP-low/Neg and CIMP-high (CIMP-H) tumors, the summary OR value was 0.77 versus 10.49, (3) distribution of KRAS/BRAF mutations in MSI-low (MSI-L)/microsatellite stable (MSS) and MSI-high (MSI-H) tumors, the summary OR value was 0.51 versus 9.60, (4) proportion of CIMP-H/MSI-H tumors among distal and proximal colorectal tumors, the summary OR value was 3.66 versus 6.54, and (5) proportion of CIMP-H tumors among MSI-L/MSS and MSI-H tumors, the summary OR value was 5.87.
Paradoxical activation of MEK/ERK signaling induced by B-Raf inhibition enhances DR5 expression and DR5 activation-induced apoptosis in Ras-mutant cancer cells.
This article reviews the current knowledge on the use and implications of BRAF mutational status in colorectal tumors, in order to define its present role in the clinical practice.
Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer.
TRAP1 is involved in BRAF regulation and downstream attenuation of ERK phosphorylation and cell-cycle progression: a novel target for BRAF-mutated colorectal tumors.
However, genomic, epigenomic and molecular pathology testings (for example, analyses for microsatellite instability, MLH1 promoter CpG island methylation, and KRAS and BRAF mutations in colorectal tumors) are becoming routine clinical practices.
To verify the technical characteristics of the microarray system for the correct identification of the KRAS mutational status at the two hotspot codons 12 and 13 and of the BRAF(V600E) mutation in colorectal tumor, we selected 75 samples previously characterized by conventional and CO-amplification at Lower Denaturation temperature-PCR (COLD-PCR) followed by High Resolution Melting analysis and direct sequencing.